Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE\xae: a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial

Hung-Ta H Wu,Chia-Chu Tsai,Chen-Te Wu,Chih-Chien Hu,Yuhan Chang,Yi-Pei Hung,Chun-Shin Chang,Cheng-Fong Chen

doi:10.1186/s13287-021-02631-z

Abstract

ObjectiveTo evaluate the safety and efficacy of intra-articular (IA) injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE® for knee osteoarthritis.MethodsThis was a patient-blind, randomized, active-control trial consisted of 4 arms including hyaluronic acid (HA) control and 3 ELIXCYTE® doses. A total of 64 subjects were screened, and 57 subjects were randomized. The primary endpoints included the changes from baseline to post-treatment visit of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at Week 24 and the incidence of adverse events (AEs) and serious adverse events (SAEs).ResultsNo ELIXCYTE®-related serious adverse events were reported during 96 weeks of follow-up and no suspected unexpected serious adverse reaction (SUSAR) or death was reported. The changes of the primary endpoint, WOMAC pain score at Week 24, showed significant differences in all ELIXCYTE® groups, as well as in HA groups between post-treatment visit and baseline. The ELIXCYTE® groups revealed significant decreases at Week 4 compared to HA group in WOMAC total scores, stiffness scores, functional limitation scores suggested the potential of ELIXCYTE® in earlier onset compared to those from HA. The significant differences of visual analog scale (VAS) pain score and Knee Society Clinical Rating System (KSCRS) functional activities score at Week 48 after ELIXCYTE® administration suggested the potential of ELIXCYTE® in the longer duration of the effectiveness compared to HA group.ConclusionsELIXCYTE® for knee osteoarthritis treatment was effective, safe, and well-tolerated. The efficacy results were showed that ELIXCYTE® conferred the earlier onset of reductions in pain scores and improvements in functional scores than HA group.Trial registration: ClinicalTrials.gov Identifier: NCT02784964. Registered 16 May, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02784964

Highlights

Knee osteoarthritis (KOA) is a chronic musculoskeletal disease that affects 7% of the global population, more than 500 million people, and has been recognized as the 15th highest cause of years lived with disability (YLDs) worldwide [1]
Novel findings on the mechanisms underlying the development of KOA promote the research of potential disease-modifying osteoarthritis drugs (DMOADs) which targeting osteoarthritis pathogenesis, such as cartilage destruction, subchondral bone remodeling, and synovial inflammation
No particular differences between individual ELIXCYTE® dose and Hyaluronic acid (HA) groups were observed in demographic data and KOA history

Summary

Introduction

Knee osteoarthritis (KOA) is a chronic musculoskeletal disease that affects 7% of the global population, more than 500 million people, and has been recognized as the 15th highest cause of years lived with disability (YLDs) worldwide [1]. Nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and corticosteroids are generally used, and patients are unsatisfied with their limited analgesic, short-term efficacy, and potential risk of gastrointestinal and cardiovascular disorder [2, 3]. Novel findings on the mechanisms underlying the development of KOA promote the research of potential disease-modifying osteoarthritis drugs (DMOADs) which targeting osteoarthritis pathogenesis, such as cartilage destruction, subchondral bone remodeling, and synovial inflammation. These DMOADs are pursued to relief pain and improve joint function, and inhibit the progression of structural disorder [5]. Even if no DMOADs have been licensed, several potential candidates are under development [2, 5]

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